Vincoleukoblastine (VLB, vinblastine) was the first of the dimeric indole alkaloids to be used in the treatment of malignancies. The compound is the subject of U.S. Pat. No. 3,097,137, to Beer, Cutts and Noble. The next of the dimeric indole alkaloids to be used in the treatment of malignancies, and in particular of the acute leukemias of childhood, was leurocristine (vincristine)--see U.S. Pat. No. 3,205,220 to Svoboda, Barnes and Armstrong. Also claimed in this latter patent was the dimeric vinca alkaloid, leurosidine, an isomer of VLB. VLB, vincristine, and leurosidine can all be represented by Formula I below as follows: ##STR1##
In Formula I, when R is formyl, R' is ethyl, and R" is hydroxy, the resulting compound is vincristine; when R is methyl, R' is ethyl, and R" is hydroxy, the compound is VLB. Leurosidine, being a C-4' epimer of vinblastine, is represented by Formula I when R is methyl, R' is hydroxy, and R" is ehtyl. Originally, leurosidine was thought to have a structure isomeric (rather than epimeric) with VLB in that the hydroxyl group was believed to be at 3' rather than 4'--see Neuss, Huckstep, and Cone, Tetrahedron Letters, 811, (1967). More recently, however, Wenkert et al. publishing in Helvetica Chimica Acta, 58, 1560 (1975) have shown that leurosidine is not the 3'-hydroxy isomer of VLB but is the 4' epimer having an .alpha.-hydroxyl and a .beta.-ethyl group.
Recently, we have invented a process for converting VLB to leurosidine by forming a 4'-bis-sulfite ester of VLB and then reacting this ester with silver perchlorate to form VLB perchlorate. This process is disclosed in our copending application Ser. No. 687,274, filed Jan. 17, 1976.
Functional derivatives of VLB, vincristine or leurosidine at 5' are not known.